Population study of allelic diversity in the human MHC class I-related MIC-A gene |
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Authors: | E. W. Petersdorf Klaus B. Shuler Gary M. Longton Thomas Spies John A. Hansen |
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Affiliation: | (1) Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. North, Seattle, WA 98109-1024, USA e-mail: epetersd@fhcrc.org, Tel.: +1-206-6675244, Fax: +1-206-6675255, US |
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Abstract: | The polymorphism of major histocompatibility complex (MHC) class I HLA-A, -B, and -C molecules may have evolved through pathogen-driven selection of alleles with diverse peptide-binding specificities. Two MHC-encoded molecules that are distantly related to class I, MIC-A and MIC-B, do not function in the presentation of pathogen-derived peptides to T cells with αβ T-cell receptors (TCRs), but are broadly recognized by intraepithelial T cells with γδ TCRs. However, both MIC-A and MIC-B are polymorphic, displaying an unusual distribution of a number of variant amino acids in their extracellular α1, α2, and α3 domains. In order to further define the polymorphism of MIC-A, we examined its alleles among 275 individuals with common and rare HLA genotypes. Of 16 previously defined alleles, 12 were confirmed and 5 new alleles were identified. A two-by-two analysis of MIC-A and HLA-B alleles uncovered a number of statistically significant associations. These results confirm and extend previous knowledge on the polymorphism of MIC-A. The strong positive linkage of certain MIC-A and HLA-B alleles may have implications for studies related to MHC-associated diseases and transplantation. Received: 5 August 1998 / Revised: 26 October 1998 |
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Keywords: | MIC-A gene Allelic diversity Allelic frequencies HLA-B Linkage disequilibrium |
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